There is a need for a liquid ophthalmic drug delivery system which is administrable to the eye in convenient drop form and which at the same time provides a prolonged ocular residence of the topically administered drug so as to maximize the topical duration of action and minimize any systemic effects.
As is well-known in the art, there is little chance of absorption of an ophthalmic drug administered to the eye in view of the fast turnover of tear fluid resulting in the drug being rapidly drained away from the eye. Therefore a vehicle is required which remains in the ocular area and retains the ophthalmic drug for a slow release thereof.
The present invention relates to the finding that an advantageous prolonged and sustained release of ophthalmic drugs into the eye can be achieved with a chitosan containing liquid ophthalmic aqueous formulation thereof which is administered at a pH of from about 3.0 to 6.2 in convenient drop form.
Chitin is a naturally occurring biopolymer of monomeric .beta.(1.fwdarw.4)-N-acetyl-D-glucosamine linked units of varying molecular weight. N-deacetylation of chitin leads to chitosan, e.g. as described in U.S. Pat. No. 3,911,098 which is incorporated herein by reference.
Chitosan is partially to substantially deacetylated chitin, and in contrast to chitin contains free amine (NH.sub.2) groups along the polymer chain.
Chitosan is, due to the presence of the free amine groups which can be protonated under acidic conditions, classified as a cationic polymer. According to U.S. Pat. No. 3,953,608, chitosan "presents the major drawback of being insoluble in an alkaline medium ". There is no appreciation or suggestion in the art that the insolubility of chitosan in an alkaline medium can in fact be used to advantage for the preparation of ophthalmic formulations so as to provide a sustained release of ophthalmic treating agents into the eye.